Exogenous Ketone Supplementation in Females With Polycystic Ovary Syndrome

PCOS Clinical Trial

Official title:

Exogenous Ketone Supplementation to Improve Cardiovascular Disease Risk Factors in Females With Polycystic Ovary Syndrome

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06155708
• Other study ID #: 2024-9710
• Status: Not yet recruiting
• Phase: N/A
• Start date: January 2024
• Est. completion date: December 2027

Study information

• Verified date: December 2023
• Source: McGill University
• Contact: Charlotte Usselman, Ph.D
• Phone: 5143962140
• Email: charlotte.usselman[@]mcgill.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Polycystic ovary syndrome (PCOS) affects 1 in 5 females of reproductive age. Commonly characterized as a disorder of infertility, PCOS is often accompanied by 3 potent cardiovascular disease (CVD) risk factors: insulin resistance, endothelial dysfunction, and elevated blood pressure. Accordingly, PCOS is associated with the development of CVD, the second leading cause of death in females in Canada. However, effective treatments to improve cardiovascular health in PCOS are lacking.

Exogenous ketone monoester (KME) ingestion has been shown to improves outcomes associated with insulin resistance, endothelial function, and blood pressure regulation in healthy individuals and individuals predisposed to CVD. Therefore, oral ketone supplements offer a practical and effective strategy for improving cardiovascular health; however, this treatment has yet to be evaluated in PCOS.

Therefore, the overall goal of this project is to employ KME ingestion to improve markers of cardiovascular health in females with PCOS.

On two different days, participants will consume either a beverage containing a ketone supplement or a beverage containing a placebo supplement. The objectives are to compare responses between KME and placebo ingestion, and examine all outcomes related to cardiovascular health in females with PCOS in comparison with female controls of similar age and body mass index. The effects of KME ingestion will be quantified on: 1) glycemic control during an oral glucose tolerance test; 2) endothelial function using the flow-mediated dilation test; 3) blood pressure and acute blood pressure regulation; and 4) hemodynamic responses to acute exercise.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 60
• Est. completion date: December 2027
• Est. primary completion date: June 2027
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 40 Years

Eligibility

Inclusion Criteria:

• All female participants will report female sex assigned at birth

• All participants will be aged 18 to 40

• PCOS diagnosis

Exclusion Criteria:

• Current smokers or a prolonged history of smoking

• Presence or history of overt cardiometabolic disease (e.g., stage 2 hypertension, diabetes, heart disease), neurologic disease, or endocrinopathy (with the exception of PCOS)

• Current pregnancy or currently breastfeeding

• Current use of medications which may affect our outcomes of interest (e.g., anti-hypertensives, anti-androgens, metformin)

Related Conditions & MeSH terms

• PCOS
• Polycystic Ovary Syndrome

Intervention

Dietary Supplement:
• Ketone
- Ketone monoester supplement in the form of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate based on participants' body weight (0.45ml/kg body weight) ingested with water and vanilla-flavored stevia in a total volume of 100 ml.
• Water
100 ml water combined with 10ml bitter flavor and vanilla-flavored stevia

Locations

Country	Name	City	State
Canada	Cardiovascular Health and Autonomic Research Laboratory	Montréal	Quebec

Sponsors (1)

Lead Sponsor	Collaborator
McGill University

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Glycemic responses to a 2-hr oral glucose tolerance test	- Glucose is calculated by the area under the curve using the trapezoid method.	0-2.5 hours in the post-prandial period
Primary	Flow mediated dilation (FMD)	- Endothelial function is assessed using the standard FMD; quantified as the percent increase in diameter from rest to peak diameter observed during reactive hyperemia (%FMD). The % change in diameter reflects the ability of the vessel to dilate in response to sheer stress induced by the flow following the release of occlusion. This reflects the function of the endothelium, or release of nitric oxide.	30 minutes
Primary	Systolic Blood Pressure (SBP)	- SBP, measured in mmHg	2 hours
Primary	Diastolic Blood Pressure (DBP)	- DBP, measured in mmHg	2 hours
Secondary	Insulin area under the curve	- Insulin area under the curve during oral glucose tolerance test	0-2.5 hours in the post-prandial period
Secondary	C-peptide	- C-peptide area under the curve during oral glucose tolerance test	0-2.5 hours in the post-prandial period
Secondary	Glucagon-like peptide-1 (GLP-1)	- GLP-1 area under the curve during oral glucose tolerance test.	0-2.5 hours in the post-prandial period
Secondary	Glucose-dependent insulinotropic polypeptide (GIP)	- GIP area under the curve during oral glucose tolerance test.	0-2.5 hours in the post-prandial period
Secondary	Triglycerides	- Triglycerides area under the curve during oral glucose tolerance test	0-2.5 hours in the post-prandial period
Secondary	Insulinogenic index	- (Insulin at 30 min - fasting insulin)/ (plasma glucose at 30 min- fasting plasma glucose).	0-2.5 hours in the post-prandial period
Secondary	Arterial artery blood flow	- Calculated as the product of mean blood flow velocity (cm/sec) and cross-sectional area (2?r2) x 60 sec/min.	0-2.5 hours in the post-prandial period
Secondary	Shear rate and low-flow mediated vasoconstriction to the FMD	- Shear rate calculated as area under the curve from cuff deflation to the time of peak dilation using the trapezoidal rule, as well as low flow-mediated vasoconstriction during forearm occlusion, which provides an index of the endothelial contribution to resting vascular tone and which predicts cardiovascular disease risk.	30 minutes
Secondary	Muscle sympathetic nerve activity (MSNA)	- Measured using microneurography, and expressed in burst/min or bursts/100 heart beats	2 hours
Secondary	Neurovascular transduction	- Assessed by the MSNA signal (recorded in both raw and filtered/rectified/integrated formats for subsequent analyses) and arterial blood flow extracted on a beat-by-beat basis and processed using custom transduction software.	2 hours
Secondary	Vascular resistance	- Calculated as mean arterial pressure divided by Finometer-derived cardiac output	2 hours
Secondary	Capillary blood Beta-OHB concentrations	- Measures in mmol/L	0-2.5 hours in the post-prandial period
Secondary	Serum testosterone	- Measured in pg/ml.	5 minutes
Secondary	Serum sex hormone binding globulin	- Measured in pg/ml.	5 minutes
Secondary	Serum estradiol	- Measured in pg/ml.	5 minutes
Secondary	Serum Progesterone	- Measured in pg/ml.	5 minutes